Towards optimal treatment selection for borderline personality disorder patients (BOOTS): a study protocol for a multicenter randomized clinical trial comparing schema therapy and dialectical behavior therapy.

BACKGROUND: Specialized evidence-based treatments have been developed and evaluated for borderline personality disorder (BPD), including Dialectical Behavior Therapy (DBT) and Schema Therapy (ST). Individual differences in treatment response to both ST and DBT have been observed across studies, but the factors driving these differences are largely unknown. Understanding which treatment works best for whom and why remain central issues in psychotherapy research. The aim of the present study is to improve treatment response of DBT and ST for BPD patients by a) identifying patient characteristics that predict (differential) treatment response (i.e., treatment selection) and b) understanding how both treatments lead to change (i.e., mechanisms of change). Moreover, the clinical effectiveness and cost-effectiveness of DBT and ST will be evaluated. METHODS: The BOOTS trial is a multicenter randomized clinical trial conducted in a routine clinical setting in several outpatient clinics in the Netherlands. We aim to recruit 200 participants, to be randomized to DBT or ST. Patients receive a combined program of individual and group sessions for a maximum duration of 25 months. Data are collected at baseline until three-year follow-up. Candidate predictors of (differential) treatment response have been selected based on the literature, a patient representative of the Borderline Foundation of the Netherlands, and semi-structured interviews among 18 expert clinicians. In addition, BPD-treatment-specific (ST: beliefs and schema modes; DBT: emotion regulation and skills use), BPD-treatment-generic (therapeutic environment characterized by genuineness, safety, and equality), and non-specific (attachment and therapeutic alliance) mechanisms of change are assessed. The primary outcome measure is change in BPD manifestations. Secondary outcome measures include functioning, additional self-reported symptoms, and well-being. DISCUSSION: The current study contributes to the optimization of treatments for BPD patients by extending our knowledge on "Which treatment - DBT or ST - works the best for which BPD patient, and why?", which is likely to yield important benefits for both BPD patients (e.g., prevention of overtreatment and potential harm of treatments) and society (e.g., increased economic productivity of patients and efficient use of treatments). TRIAL REGISTRATION: Netherlands Trial Register, NL7699 , registered 25/04/2019 - retrospectively registered.

Deep learning architectures analysis for age-related macular degeneration segmentation on optical coherence tomography scans.

BACKGROUND AND OBJECTIVES: Aged people usually are more to be diagnosed with retinal diseases in developed countries. Retinal capillaries leakage into the retina swells and causes an acute vision loss, which is called age-related macular degeneration (AMD). The disease can not be adequately diagnosed solely using fundus images as depth information is not available. The variations in retina volume assist in monitoring ophthalmological abnormalities. Therefore, high-fidelity AMD segmentation in optical coherence tomography (OCT) imaging modality has raised the attention of researchers as well as those of the medical doctors. Many methods across the years encompassing machine learning approaches and convolutional neural networks (CNN) strategies have been proposed for object detection and image segmentation. METHODS: In this paper, we analyze four wide-spread deep learning models designed for the segmentation of three retinal fluids outputting dense predictions in the RETOUCH challenge data. We aim to demonstrate how a patch-based approach could push the performance for each method. Besides, we also evaluate the methods using the OPTIMA challenge dataset for generalizing network performance. The analysis is driven into two sections: the comparison between the four approaches and the significance of patching the images. RESULTS: The performance of networks trained on the RETOUCH dataset is higher than human performance. The analysis further generalized the performance of the best network obtained by fine-tuning it and achieved a mean Dice similarity coefficient (DSC) of 0.85. Out of the three types of fluids, intraretinal fluid (IRF) is more recognized, and the highest DSC value of 0.922 is achieved using Spectralis dataset. Additionally, the highest average DSC score is 0.84, which is achieved by PaDeeplabv3+ model using Cirrus dataset. CONCLUSIONS: The proposed method segments the three fluids in the retina with high DSC value. Fine-tuning the networks trained on the RETOUCH dataset makes the network perform better and faster than training from scratch. Enriching the networks with inputting a variety of shapes by extracting patches helped to segment the fluids better than using a full image.

[Diagnostic performance of imaging examinations in acute non-traumatic abdominal pain in the radiology department of the Kaolack Regional Hospital]. / Apport de l'imagerie dans la prise en charge des douleurs abdominales aigues non traumatiques au Centre Hospitalier Regional de Kaolack.

AIM: The aim of this work was to evaluate the diagnostic performance of imaging examinations in the presence of acute non-traumatic abdominal pain. MATERIALS AND METHODS: This was a prospective, cross-sectional and descriptive study over 6 months in the radiology and medical imaging department of the Kaolack Regional Hospital, including any patient received for acute non-traumatic abdominal pain with informed consent in whom the etiological diagnosis is supported by an imaging examination. We investigated the etiologies of acute abdominal pain and compared the imaging findings with surgical exploration. Our data were analyzed using SPSS 24.0 and Excel 2013 with a coefficient of significance of less than 5%. RESULTS: 106 patients were enrolled. The mean age was 32 years and the gender-ratio was 1.52 in favour of women. Acute abdominal pain was diffuse in 25.5% of patients and localized in 74.5%, of which 18.9% were at right iliac fossa.Abdominal X-ray was performed alone in 4 patients (3.8%), ultrasound alone in 46 patients (43.3%) and abdominal CT scan in 34 patients (32%). CT was combined with ultrasound in 6 patients (5.7%) and with abdominal X-ray in 16 patients (15%). The initial clinical diagnosis was corrected in 49.1% of patients. The sensitivity of the imaging compared to the final diagnosis retained was 96.2%. CONCLUSION: Imaging represents a turning point in the management of patients with acute non-traumatic abdominal pain by providing better diagnostic guidance and avoiding serious complications and unnecessary interventions.

BUT: le but de ce travail était d'évaluer les performances diagnostiques des examens d'imagerie devant des douleurs abdominales aigües non traumatiques. MATÉRIELS ET MÉTHODES: il s'agissait d'une étude prospective, transversale et descriptive sur 06 mois dans le service de radiologie et imagerie médicale de l'hôpital régional de Kaolack, incluant tout patient reçu pour douleur abdominale aigue non traumatique avec son consentement éclairé chez qui le diagnostic étiologique est appuyé par un examen d'imagerie. Nous avons recherché les étiologies des douleurs abdominales aigues et confronter les résultats de l'imagerie à l'exploration chirurgicale. Nos données ont été analysés avec les logiciels SPSS 24.0 et Excel 2013 avec un coefficient de significativité inférieur à 5%. RÉSULTATS: 106 patients ont été retenu. L'âge moyen était de 32 ans et le genre-ratio de 1,52 en faveur des femmes. La douleur abdominale aigüe était diffuse chez 25,5% des patients et localisée chez 74,5% dont 18,9% à la FID. L'ASP a été réalisé seul chez 4 patients (3,8%), l'échographie seule chez 46 patients (43,3%) et le scanner abdominal chez 34 patients (32%). Le scanner a été couplé à l'échographie chez 6 patients (5,7%) et avec l'ASP chez 16 patients (15%). Le diagnostic clinique initial a été rectifié chez 49,1% des patients. La sensibilité de l'imagerie par rapport au diagnostic final retenu était de 96,2%. CONCLUSION: L'imagerie constitue un tournant décisif dans la prise en charge des patients présentant une douleur abdominale aigüe non traumatique en apportant une meilleure orientation diagnostique évitant aux patients des complications graves et des interventions inutiles.

Hemolin: an insect-immune protein belonging to the immunoglobulin superfamily.

Insects have an efficient defense system against infections. Their antibacterial immune proteins have been well characterized. However, the molecular mechanisms by which insects recognize foreignness are not yet known. Data are presented showing that hemolin (previously named P4), a bacteria-inducible hemolymph protein of the giant silk moth Hyalophora cecropia, belongs to the immunoglobulin superfamily. Functional analyses indicate that hemolin is one of the first hemolymph components to bind to the bacterial surface, taking part in a protein complex formation that is likely to initiate the immune response.

Crystal structure of hemolin: a horseshoe shape with implications for homophilic adhesion.

Hemolin, an insect immunoglobulin superfamily member, is a lipopolysaccharide-binding immune protein induced during bacterial infection. The 3.1 angstrom crystal structure reveals a bound phosphate and patches of positive charge, which may represent the lipopolysaccharide binding site, and a new and unexpected arrangement of four immunoglobulin-like domains forming a horseshoe. Sequence analysis and analytical ultracentrifugation suggest that the domain arrangement is a feature of the L1 family of neural cell adhesion molecules related to hemolin. These results are relevant to interpretation of human L1 mutations in neurological diseases and suggest a domain swapping model for how L1 family proteins mediate homophilic adhesion.

Oviposition responses of Anopheles gambiae s.s. (Diptera: Culicidae) and identification of volatiles from bacteria-containing solutions.

In this study, a dual-choice oviposition bioassay was used to screen responses of gravid An. gambiae toward 17 bacterial species, previously isolated from Anopheles gambiae s.l. (Diptera: Culicidae) midguts or oviposition sites. The 10 isolates from oviposition sites have been identified by phylogenetic analyses of their 16S rRNA genes. Eight of the 10 isolates were gram-positive, out of which six belonged to the Bacilli class. Solid phase microextraction and gas chromatography coupled to mass spectrometry (GC-MS) were used to identify the volatiles emitted from the bacterial isolates. Aromatic and aliphatic alcohols, aliphatic ketones, alkylpyrazines, dimethyl oligosulfides, and indole were among the chemical compounds identified from the headspace above bacteria-containing saline. The mosquitoes laid significantly more eggs in six of the bacteria-containing solutions compared with the sterile solution. These six bacteria did not emit any compounds in common that could explain the positive oviposition response. Instead, the bacteria were grouped according to principal component analysis (PCA) based on the relative amounts of volatiles emitted. The PCA-plots facilitated the identification of 13 putative oviposition attractants for An. gambiae mosquitoes.

Re-introducing bacteria in mosquitoes--a method for determination of mosquito feeding preferences based on coloured sugar solutions.

In this study, sugar-feeding was investigated as a possible means of re-introducing bacteria into mosquito midguts with the aim of identifying bacteria that are suitable for creating paratransgenic mosquitoes. In a paratransgenic approach, bacteria are utilised to deliver effector molecules capable of inhibiting pathogen development in the midgut of the vector. To determine if mosquitoes discriminate between sterile sugar solutions and sugar solutions with bacteria, a method for screening mosquito feeding preferences was developed. This method was tested for Aedes aegypti, Anopheles arabiensis and An. gambiae s.s. mosquitoes and is based on a dual-choice test of solutions labelled with food dyes. Three different tests (dye/colour detection, sugar detection and sugar-concentration detection) were performed to evaluate the method, after which bacteria previously isolated from mosquitoes were used in the experiments. It was shown that mosquitoes do not discriminate between sugar solutions with or without these bacteria indicating that sugar-feeding is a possible means to introduce bacteria into mosquitoes. Furthermore, two different setups of the method were used, enabling us to differentiate between tactile/taste and olfactory responses. The method described in this paper is easy to use, cost-effective and allows broad screening of mosquito sugar-feeding preferences.

kappa B-like motifs regulate the induction of immune genes in Drosophila.

The mammalian transcription factor NF-kappa B regulates a number of genes involved in immune and acute phase responses, by interacting with a nucleotide sequence element, the kappa B-motif. In this work we demonstrate the participation of similar motifs in the immune response of insects as well: kappa B-like motifs have a regulatory role in the synthesis of cecropins, a set of anti-bacterial peptides, triggered by the presence of bacterial cell wall components in the insect blood. We show that the upstream region of the Cecropin gene CecA1 contains elements responsible for inducible and tissue-specific expression. Furthermore, a trimer of kappa B-like motif confers high levels of inducible expression from the reporter gene, after transfection in a Drosophila blood cell line. As in the moth Hyalophora cecropia, stimulation with bacterial lipopolysaccharide induces a nuclear factor that specifically binds to the kappa B-like motif. Our data suggest a functional and evolutionary relationship between these insect immune response factors and the mammalian NF-kappa B.

The insect immune protein hemolin is expressed during oogenesis and embryogenesis.

Hemolin is the most abundant bacteria-induced proteins in Hyalophora cecropia hemolymph. Its structural features, both at the protein and gene level, ascribe this molecule to the immunoglobulin gene superfamily (IgSF) with particular homology to neural cell adhesion molecules. An increasing number of evidence suggest a role in immune recognition and in cell adhesion events. Hemolin is also developmentally regulated as suggested by changes in its concentration during larval and pupal ecdysis (Trenczek, T., 1998. Endogenous defense mechanisms of insects. Zoology 101, 298-315; Lanz-Mendoza, H., Faye, I., 1999. Physiological aspects of the immunoglobulin superfamily in invertebrates. Dev. Comp. Immunol. 23, 359-374). In the present study the expression of hemolin was investigated in oogenesis and in early embryogenesis. Our results reveal that hemolin is expressed in follicles and in epidermal and neural tissues of embryos.

Lipopolysaccharide interaction with hemolin, an insect member of the Ig-superfamily.

This study is an attempt to reach some understanding of how insects recognize intruding microorganisms and foreign entities while executing an immune response. We used lipopolysaccharide (LPS) from Escherichia coli, bound to a radiolabeled iodinated crosslinker, to identify hemolymph proteins from the Hyalophora cecropia moth that have the capacity to bind LPS. High amounts of radioactivity were conferred to hemolin, an immunoglobulin and NCAM-related protein, the concentration of which increases in insect hemolymph upon bacterial infection. We could demonstrate a concentration-dependent binding of hemolin to LPS. In addition we could show that Lipid A can compete for this binding, whereas KDO has no effect, indicating that hemolin interacts specifically with the Lipid A moiety of LPS.

Specific immune recognition of insect hemolin.

Bacteria entering the body cavities of insects are recognized by hemolymph components and subsequently inactivated by phagocytosis and nodule formation. A hemolymph component called hemolin is apparently involved in the recognition process. It binds to a bacterial surface molecule and forms a stable complex with other hemolymph proteins. Hemolin binding is independent of bacterial lipopolysaccharide (LPS) structure, whereas the complex formation is dependent on the presence of the carbohydrate moiety of LPS molecules. The specificity of immune recognition in insects is discussed.

On the primary structures of lysozyme, cecropins and attacins from Hyalophora cecropia.

Diapausing pupae of Cecropia respond to a bacterial infection by the selective synthesis of RNA and 15-20 hemolymph proteins. Of these we have purified lysozyme and two classes of antibacterial proteins called cecropins and attacins. The primary structure has been determined for the lysozyme, one attacin and five cecropins. We have also prepared a cDNA bank, isolated and sequenced clones corresponding to the lysozyme, the two main attacins and one cecropin. The results of these structural studies are briefly summarized. Finally we review the solid phase synthesis of cecropin A and B and 9 analogs of cecropin A.

[Cryptosporidiosis among intestinal parasitosis in Senegalese pediatric hospital patients]. / Place de la cryptosporidiose au sein des parasitoses intestinales en milieu hospitalier pédiatrique sénégalais.

From November 1991 to March 1992 authors have carried out a study on the place of cryptosporidiosis among the intestinal diseases in children from a Dakar Pediatric Hospital. Different technics have been used to identify the parasites in the stool: direct examination, followed by Ritchie and Zielh Nielsen modified by Henricksen and Poblenz. The results show that 32% of the children were carriers parasites. Helminths represent 53.2% of the parasites with predominance of Ascaris lumbricoides. Giardia intestinalis is the more representative parasite among the Protozoa which constitute 46.8% of the parasites. 13 cases of parasites associations have been founded. The cryptosporidies have been founded in 3 stools, and constitute 4.6% of the whole parasites. The cryptosporidiosis take a little place among the intestinal diseases in Dakar's children.

Disaster readiness for nurses in the workplace: preparing for the Zombie Apocalypse.

The Centers for Disease Control and Prevention (CDC) urges citizens everywhere to prepare for any emergency that might occur in their areas. In conjunction with the U.S. Federal Emergency Management Agency and the U.S. Department of Homeland Security, the CDC has designed a four-step plan ("Ready America") to assist all Americans in taking action. As the largest body of health care providers, nurses across the nation have the potential to contribute substantially to disaster readiness in the workplace and the community. This article reviews lessons learned from previous disasters and also presents an overview of ethical-legal considerations related to disaster nursing care. In addition, a preparation guide for nurses in the workplace and on the home front is presented. Disaster preparation resources are also provided.

Transstadial and horizontal transfer of bacteria within a colony of Anopheles gambiae (Diptera: Culicidae) and oviposition response to bacteria-containing water.

In a paratransgenic approach, genetically modified bacteria are utilized to kill the parasite in the vector gut. A critical component for paratransgenics against malaria is how transgenic bacteria can be introduced and then kept in a mosquito population. Here, we investigated transstadial and horizontal transfer of bacteria within an Anopheles gambiae mosquito colony with the focus on spiked breeding sites as a possible means of introducing bacteria to mosquitoes. A Pantoea stewartii strain, previously isolated from An. gambiae, marked with a green fluorescent protein (GFP), was introduced to mosquitoes in different life stages. The following life stages or older mosquitoes in the case of adults were screened for bacteria in their guts. In addition to P. stewartii other bacteria were isolated from the guts: these were identified by 16S rRNA sequence analysis and temporal temperature gradient gel electrophoresis (TTGE). Bacteria were transferred from larvae to pupae but not from pupae to adults. The mosquitoes were able to take up bacteria from the water they emerged from and transfer the same bacteria to the water they laid eggs in. Elizabethkingia meningoseptica was more often isolated from adult mosquitoes than P. stewartii. A bioassay was used to examine An. gambiae oviposition responses towards bacteria-containing solutions. The volatiles emitted from the solutions were sampled by headspace-solid phase microextraction (SPME) and identified by gas chromatography and mass spectrometry (GC-MS) analysis. P. stewartii but not E. meningoseptica mediated a positive oviposition response. The volatiles emitted by P. stewartii include indole and 3-methyl-1-butanol, which previously have been shown to affect An. gambiae mosquito behaviour. E. meningoseptica emitted indole but not 3-methyl-1-butanol, when suspended in saline. Taken together, this indicates that it may be possible to create attractive breeding sites for distribution of genetically modified bacteria in the field in a paratransgenic approach against malaria. Further research is needed to determine if the bacteria are also transferred in the same way in nature.

20-Hydroxyecdysone indirectly regulates Hemolin gene expression in Hyalophora cecropia.

Development and innate immune defence are two vital processes that have been demonstrated to use the same or similar molecules and signalling pathways in insects. Hemolin is a moth haemolymph protein belonging to the immunoglobulin superfamily. It is strongly induced upon bacterial infection. However, recent studies indicate a developmental regulation of hemolin. We show that the steroid hormone 20-hydroxyecdysone (20E) can activate the expression of Hyalophora cecropia Hemolin (HcHemolin) in the fat body of diapausing pupae. Using the protein synthesis inhibitor cycloheximide we demonstrate that Hemolin up-regulation by 20E requires ongoing protein synthesis. Moreover, 20E enhances transcription of the Hemolin gene in response to bacteria. Comparing the upstream regions of Manduca sexta Hemolin (MsHemolin) and HcHemolin, we identified four putative regulatory sites. Two are putative hormone response elements (HREs), one with an imperfect inverted repeat (HRE-IR) and one with a monomeric site (HRE-M). An additional monomeric hormone receptor site (MRE) is present only in HcHemolin. The third conserved motif is similar to the interferon (IFN) regulatory factor binding element (IRF-E) and IFN-stimulated response element (ISRE). The fourth conserved element is a kappaB motif situated between the Cap-site and the TATA-box. Finally, by electrophoresis mobility shift assay we demonstrate that the HRE-IR forms specific complexes with nuclear extract proteins of normal pupae that increase after 20E stimulation.

Hemolin gene silencing by ds-RNA injected into Cecropia pupae is lethal to next generation embryos.

There is increasing evidence of an intimate connection between participants in the innate immune system and in development. Molecules involved in the determination of dorso-ventral polarity in Drosophila have related counterparts in the signalling pathways for immune gene activation in both insects and mammals. Hemolin from the Giant silkmoth, Hyalophora cecropia, identified as a bacteria-inducible molecule and a member of the immunoglobulin superfamily, is present as protein and transcripts in oocytes and embryos. We used RNA interference (RNAi) to investigate H. cecropia gene function in vivo and demonstrated that Hemolin is crucial for the normal development of embryos. When RNAi-females were mated, no larvae emerged from their eggs and when dissected, the eggs revealed malformed embryos. Western blot analysis confirmed the lack of Hemolin gene products. We conclude that Hemolin is necessary for development, since the silencing of Hemolin gene expression leads to embryonic lethality.